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. 1997 Oct;92(2):214–219. doi: 10.1046/j.1365-2567.1997.00336.x

L-selectin activates JNK via src-like tyrosine kinases and the small G-protein Rac.

B Brenner 1, S Weinmann 1, H Grassmé 1, F Lang 1, O Linderkamp 1, E Gulbins 1
PMCID: PMC1364061  PMID: 9415029

Abstract

Selectin and alpha 4 beta 7-integrins have been shown to mediate transient leucocyte interactions with endothelial cells which is a crucial step in the initial immune response to pathogens. We have previously shown that stimulation of T lymphocytes via L-selectin results in activation of a signalling cascade from the L-selectin molecule via the tyrosine kinase p56lck and tyrosine phosphorylation of L-selectin to the stimulation of p21Ras and Rac proteins. In the present study we demonstrate that stimulation of Jurkat T lymphocytes via L-selectin results in an activation of Jun N-terminal kinase (JNK) but not of p38-K. L-selectin-initiated activation of JNK is mediated by src-like tyrosine kinases and the small G-protein Rac 1/2, since genetic or pharmacological inhibition of p56lck or Rac proteins prevent the stimulation of JNK by L-selectin. Thus, the data point to a novel signalling cascade from L-selectin via src-like tyrosine kinases and Rac proteins to JNK.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Angel P., Karin M. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta. 1991 Dec 10;1072(2-3):129–157. doi: 10.1016/0304-419x(91)90011-9. [DOI] [PubMed] [Google Scholar]
  2. Arbonés M. L., Ord D. C., Ley K., Ratech H., Maynard-Curry C., Otten G., Capon D. J., Tedder T. F. Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. Immunity. 1994 Jul;1(4):247–260. doi: 10.1016/1074-7613(94)90076-0. [DOI] [PubMed] [Google Scholar]
  3. Bargatze R. F., Jutila M. A., Butcher E. C. Distinct roles of L-selectin and integrins alpha 4 beta 7 and LFA-1 in lymphocyte homing to Peyer's patch-HEV in situ: the multistep model confirmed and refined. Immunity. 1995 Jul;3(1):99–108. doi: 10.1016/1074-7613(95)90162-0. [DOI] [PubMed] [Google Scholar]
  4. Berman C. L., Yeo E. L., Wencel-Drake J. D., Furie B. C., Ginsberg M. H., Furie B. A platelet alpha granule membrane protein that is associated with the plasma membrane after activation. Characterization and subcellular localization of platelet activation-dependent granule-external membrane protein. J Clin Invest. 1986 Jul;78(1):130–137. doi: 10.1172/JCI112542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bevilacqua M. P., Pober J. S., Mendrick D. L., Cotran R. S., Gimbrone M. A., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. doi: 10.1073/pnas.84.24.9238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Booth W., Crawford M., Sun M. New hands on the purse strings. Science. 1989 Jan 13;243(4888):160–160. doi: 10.1126/science.2643159. [DOI] [PubMed] [Google Scholar]
  7. Bosse R., Vestweber D. Only simultaneous blocking of the L- and P-selectin completely inhibits neutrophil migration into mouse peritoneum. Eur J Immunol. 1994 Dec;24(12):3019–3024. doi: 10.1002/eji.1830241215. [DOI] [PubMed] [Google Scholar]
  8. Butcher E. C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell. 1991 Dec 20;67(6):1033–1036. doi: 10.1016/0092-8674(91)90279-8. [DOI] [PubMed] [Google Scholar]
  9. Coso O. A., Chiariello M., Yu J. C., Teramoto H., Crespo P., Xu N., Miki T., Gutkind J. S. The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell. 1995 Jun 30;81(7):1137–1146. doi: 10.1016/s0092-8674(05)80018-2. [DOI] [PubMed] [Google Scholar]
  10. Crabtree G. R. Contingent genetic regulatory events in T lymphocyte activation. Science. 1989 Jan 20;243(4889):355–361. doi: 10.1126/science.2783497. [DOI] [PubMed] [Google Scholar]
  11. Feig L. A., Cooper G. M. Inhibition of NIH 3T3 cell proliferation by a mutant ras protein with preferential affinity for GDP. Mol Cell Biol. 1988 Aug;8(8):3235–3243. doi: 10.1128/mcb.8.8.3235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gulbins E., Bissonnette R., Mahboubi A., Martin S., Nishioka W., Brunner T., Baier G., Baier-Bitterlich G., Byrd C., Lang F. FAS-induced apoptosis is mediated via a ceramide-initiated RAS signaling pathway. Immunity. 1995 Apr;2(4):341–351. doi: 10.1016/1074-7613(95)90142-6. [DOI] [PubMed] [Google Scholar]
  13. Hibi M., Lin A., Smeal T., Minden A., Karin M. Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev. 1993 Nov;7(11):2135–2148. doi: 10.1101/gad.7.11.2135. [DOI] [PubMed] [Google Scholar]
  14. Hwang S. T., Singer M. S., Giblin P. A., Yednock T. A., Bacon K. B., Simon S. I., Rosen S. D. GlyCAM-1, a physiologic ligand for L-selectin, activates beta 2 integrins on naive peripheral lymphocytes. J Exp Med. 1996 Oct 1;184(4):1343–1348. doi: 10.1084/jem.184.4.1343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jain J., McCaffrey P. G., Valge-Archer V. E., Rao A. Nuclear factor of activated T cells contains Fos and Jun. Nature. 1992 Apr 30;356(6372):801–804. doi: 10.1038/356801a0. [DOI] [PubMed] [Google Scholar]
  16. Jutila M. A., Kishimoto T. K., Butcher E. C. Regulation and lectin activity of the human neutrophil peripheral lymph node homing receptor. Blood. 1990 Jul 1;76(1):178–183. [PubMed] [Google Scholar]
  17. Jutila M. A., Rott L., Berg E. L., Butcher E. C. Function and regulation of the neutrophil MEL-14 antigen in vivo: comparison with LFA-1 and MAC-1. J Immunol. 1989 Nov 15;143(10):3318–3324. [PubMed] [Google Scholar]
  18. Kansas G. S., Ley K., Munro J. M., Tedder T. F. Regulation of leukocyte rolling and adhesion to high endothelial venules through the cytoplasmic domain of L-selectin. J Exp Med. 1993 Mar 1;177(3):833–838. doi: 10.1084/jem.177.3.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kishimoto T. K., Warnock R. A., Jutila M. A., Butcher E. C., Lane C., Anderson D. C., Smith C. W. Antibodies against human neutrophil LECAM-1 (LAM-1/Leu-8/DREG-56 antigen) and endothelial cell ELAM-1 inhibit a common CD18-independent adhesion pathway in vitro. Blood. 1991 Aug 1;78(3):805–811. [PubMed] [Google Scholar]
  20. Knaus U. G., Heyworth P. G., Evans T., Curnutte J. T., Bokoch G. M. Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science. 1991 Dec 6;254(5037):1512–1515. doi: 10.1126/science.1660188. [DOI] [PubMed] [Google Scholar]
  21. Labow M. A., Norton C. R., Rumberger J. M., Lombard-Gillooly K. M., Shuster D. J., Hubbard J., Bertko R., Knaack P. A., Terry R. W., Harbison M. L. Characterization of E-selectin-deficient mice: demonstration of overlapping function of the endothelial selectins. Immunity. 1994 Nov;1(8):709–720. doi: 10.1016/1074-7613(94)90041-8. [DOI] [PubMed] [Google Scholar]
  22. Larsen E., Celi A., Gilbert G. E., Furie B. C., Erban J. K., Bonfanti R., Wagner D. D., Furie B. PADGEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes. Cell. 1989 Oct 20;59(2):305–312. doi: 10.1016/0092-8674(89)90292-4. [DOI] [PubMed] [Google Scholar]
  23. Laudanna C., Constantin G., Baron P., Scarpini E., Scarlato G., Cabrini G., Dechecchi C., Rossi F., Cassatella M. A., Berton G. Sulfatides trigger increase of cytosolic free calcium and enhanced expression of tumor necrosis factor-alpha and interleukin-8 mRNA in human neutrophils. Evidence for a role of L-selectin as a signaling molecule. J Biol Chem. 1994 Feb 11;269(6):4021–4026. [PubMed] [Google Scholar]
  24. Ley K., Gaehtgens P., Fennie C., Singer M. S., Lasky L. A., Rosen S. D. Lectin-like cell adhesion molecule 1 mediates leukocyte rolling in mesenteric venules in vivo. Blood. 1991 Jun 15;77(12):2553–2555. [PubMed] [Google Scholar]
  25. Mayadas T. N., Johnson R. C., Rayburn H., Hynes R. O., Wagner D. D. Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice. Cell. 1993 Aug 13;74(3):541–554. doi: 10.1016/0092-8674(93)80055-j. [DOI] [PubMed] [Google Scholar]
  26. Minden A., Lin A., Claret F. X., Abo A., Karin M. Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs. Cell. 1995 Jun 30;81(7):1147–1157. doi: 10.1016/s0092-8674(05)80019-4. [DOI] [PubMed] [Google Scholar]
  27. Muegge K., Williams T. M., Kant J., Karin M., Chiu R., Schmidt A., Siebenlist U., Young H. A., Durum S. K. Interleukin-1 costimulatory activity on the interleukin-2 promoter via AP-1. Science. 1989 Oct 13;246(4927):249–251. doi: 10.1126/science.2799385. [DOI] [PubMed] [Google Scholar]
  28. Northrop J. P., Ullman K. S., Crabtree G. R. Characterization of the nuclear and cytoplasmic components of the lymphoid-specific nuclear factor of activated T cells (NF-AT) complex. J Biol Chem. 1993 Feb 5;268(4):2917–2923. [PubMed] [Google Scholar]
  29. Ridley A. J., Paterson H. F., Johnston C. L., Diekmann D., Hall A. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell. 1992 Aug 7;70(3):401–410. doi: 10.1016/0092-8674(92)90164-8. [DOI] [PubMed] [Google Scholar]
  30. Serfling E., Barthelmäs R., Pfeuffer I., Schenk B., Zarius S., Swoboda R., Mercurio F., Karin M. Ubiquitous and lymphocyte-specific factors are involved in the induction of the mouse interleukin 2 gene in T lymphocytes. EMBO J. 1989 Feb;8(2):465–473. doi: 10.1002/j.1460-2075.1989.tb03399.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Simon S. I., Burns A. R., Taylor A. D., Gopalan P. K., Lynam E. B., Sklar L. A., Smith C. W. L-selectin (CD62L) cross-linking signals neutrophil adhesive functions via the Mac-1 (CD11b/CD18) beta 2-integrin. J Immunol. 1995 Aug 1;155(3):1502–1514. [PubMed] [Google Scholar]
  32. Springer T. A. Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu Rev Physiol. 1995;57:827–872. doi: 10.1146/annurev.ph.57.030195.004143. [DOI] [PubMed] [Google Scholar]
  33. Stenberg P. E., McEver R. P., Shuman M. A., Jacques Y. V., Bainton D. F. A platelet alpha-granule membrane protein (GMP-140) is expressed on the plasma membrane after activation. J Cell Biol. 1985 Sep;101(3):880–886. doi: 10.1083/jcb.101.3.880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Su B., Jacinto E., Hibi M., Kallunki T., Karin M., Ben-Neriah Y. JNK is involved in signal integration during costimulation of T lymphocytes. Cell. 1994 Jun 3;77(5):727–736. doi: 10.1016/0092-8674(94)90056-6. [DOI] [PubMed] [Google Scholar]
  35. Watson S. R., Fennie C., Lasky L. A. Neutrophil influx into an inflammatory site inhibited by a soluble homing receptor-IgG chimaera. Nature. 1991 Jan 10;349(6305):164–167. doi: 10.1038/349164a0. [DOI] [PubMed] [Google Scholar]
  36. von Andrian U. H., Chambers J. D., McEvoy L. M., Bargatze R. F., Arfors K. E., Butcher E. C. Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and the leukocyte beta 2 integrins in vivo. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7538–7542. doi: 10.1073/pnas.88.17.7538. [DOI] [PMC free article] [PubMed] [Google Scholar]

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